DNA methylation-based estimator of telomere length

Area of Science:

• Epigenetics
• Gerontology
• Molecular Biology

Background:

• Telomere length (TL) is a known biomarker for aging and is associated with age-related diseases.
• Current methods for measuring TL, such as leukocyte TL (LTL), have limitations in their association with age and predictive power.

Purpose of the Study:

• To develop and validate a novel DNA methylation estimator of telomere length (DNAmTL) using 140 CpGs.
• To assess the performance of DNAmTL in predicting age, mortality, and age-related diseases compared to measured LTL.
• To explore the associations of DNAmTL with lifestyle factors and physical functioning.

Main Methods:

• Development of a DNA methylation-based estimator for telomere length (DNAmTL) using 140 CpG sites.
• Validation of DNAmTL across diverse populations and large-scale datasets (n=10k) including Framingham Heart Study, Women's Health Initiative, and others.
• Statistical analysis to compare DNAmTL and LTL in predicting mortality, coronary heart disease, congestive heart failure, smoking history, physical fitness, and other health indicators.

Main Results:

• Leukocyte DNAmTL demonstrated a stronger correlation with age (r ~ -0.75) than measured LTL (r ~ -0.35).
• DNAmTL significantly outperformed LTL in predicting time-to-death, time-to-coronary heart disease, time-to-congestive heart failure, and smoking history.
• DNAmTL showed significant associations with physical fitness, age-at-menopause, dietary intake, educational attainment, and income.

Conclusions:

• DNAmTL is a robust epigenetic biomarker that accurately estimates telomere length and is strongly associated with chronological age.
• DNAmTL serves as a superior predictor of mortality and age-related diseases compared to measured LTL.
• DNAmTL reflects cellular replicative history and holds potential as a biomarker for healthspan and age-related pathologies.